The objective of the work proposed in this grant is to attempt to isolate glucocorticoid antagonizing factor formed by cells of the reticuloendothelial system in response to lipopolysaccharide stimulation. It is believed to be aprotein in excess of 100,000 molecular weight since it is inactivated by pronase and by heating to 70 C for 30 min. It is now assayed in mice as an inhibitor of the induction of phosphoenolpyruvate carboxykinase by hydrocortisone. Hepatoma cells in culture will also be tested as an assay system for the factor and if this proves feasible then purification should be easier because smaller amounts of the material will be required. If the work progresses as anticipated the hepatoma cell line will be used to determine how the factor interferes with the synthesis of the above and other inducible enzymes.